Pulmonary Embolism and the Role of Echocardiograms in Management Nicholas Lee, PGY-2 March 2016

Objective Define massive vs. submassive vs. nonmassive pulmonary embolism To examine the frequency in which echocardiograms are ordered for management of pulmonary emboli in the inpatient setting Review of the guidelines regarding the role of echocardiograms in the management of pulmonary emboli

Pulmonary Embolism Massive Pulmonary Embolism Sustained hypotension SBP<90 mm Hg for at least 15 minutes or requiring pressure support Pulselessness Persistent profound bradycardia (HR <40 bpm with signs or symptoms of shock) Submassive Pulmonary Embolism Systolic blood pressure >/=90 mm Hg with evidence of RV dysfunction or myocardial necrosis Nonmassive Pulmonary Embolism Absence of clinical markers that define massive or submassive pulmonary embolism -Approximately 200,000 individuals die per year in the US secondary to pulmonary emboli -If left untreated, mortality is approximately 30% -It is important to define massive vs. submassive vs. nonmassive pulmonary embolism because it allows for risk stratification and to ensure medical and interventional therapies are tailored to the appropriate patients Jaff, M. R., McMurtry, M. S., Archer, S. L., Cushman, M., Goldenberg, N., Goldhaber, S. Z., ... & Vedantham, S. (2011). Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension a scientific statement from the American Heart Association. Circulation, 123(16), 1788-1830.

RV Dysfunction/Myocardial Necrosis Criteria RV dysfunction defined as having one of the following: RV dilation or RV dysfunction on echocardiogram RV dilation on CT Elevation of BNP (>90 pg/mL) Elevation of N-terminal pro-BNP (>500 pg/mL) EKG changes (new complete or incomplete RBBB, anteroseptal ST elevation or depression, or anteroseptal T-wave inversion) Myocardial Necrosis defined as: Elevation of troponin I (>0.4 ng/mL) or Elevation of troponin T (0.1 ng/mL) Of note, the definitions for RV dysfunction have varied across studies. These criteria were set proposed by the AHA in the following article: Jaff, M. R., McMurtry, M. S., Archer, S. L., Cushman, M., Goldenberg, N., Goldhaber, S. Z., ... & Vedantham, S. (2011). Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension a scientific statement from the American Heart Association. Circulation, 123(16), 1788-1830.

Why is this important? Risk stratification guides therapy Nonmassive PE anticoagulation alone Massive PE thrombolysis or surgical embolectomy How do we treat submassive PE? (approximately 30% of PEs) Studies have shown that RV dysfunction related to PE is associated with increased short and long term mortality up to one year after a submassive PE Why is it important to distinguish massive vs. submassive vs. nonmassive pulmonary emboli? Risk stratification is a reflection of prognosis, ultimately guiding treatment It is widely accepted that those with nonmassive pulmonary embolism be treated with anticoagulation alone and those with massive pulmonary embolism be treated with urgent thrombolysis or surgical embolectomy The main controversy revolves around how to treat those with submassive pulmonary emboli, which make up approximately 30% with pulmonary embolism Studies have shown that RV dysfunction related to pulmonary embolism is associated with increased short and long term mortality up to one year after a submassive pulmonary embolism

Inpatient Medicine Pulmonary Embolism Patient’s on the internal medicine service were reviewed daily from 2/24-3/10 to identify those admitted with a primary diagnosis of a pulmonary embolism. Only one individual was admitted to the internal medicine service with a diagnosis of a pulmonary embolism The patient was found to have multiple right subsegmental pulmonary emboli on CTA. Troponin negative. EKG within normal limits. The patient remained hemodynamically stable throughout the hospital course. An echocardiogram was not ordered. Patient treated with anticoagulation alone

Inpatient Medicine Pulmonary Embolism (Con’t) Due to the lack of cases with a primary diagnosis of PE, I reviewed a list of patients from UCI where I had been directly involved in their care from 2/2015-1/2016 and identified those with PEs. There were three individuals identified. All three were found to have multiple subsegmental pulmonary emboli. 2 individuals had bilateral involvement All three had negative Troponins. 1 had an initial EKG demonstrating an incomplete RBBB with normalization on a repeat EKG 6 hours later All remained hemodynamically stable throughout their hospital courses All three had echocardiograms ordered and they were negative for RV dysfunction From the information collected, obtaining an ECHO did not change the treatment plan for these patients.

So what is the cost conscious issue? Whether or not pursuing an echocardiogram to further stratify a patient is truly needed in every patient in the absence of hemodynamic instability, elevated troponins, dynamic EKG changes and/or clinical severity/deterioration There are inconsistencies regarding when and when not to order Cost of an echocardiogram: $1000-3000+, $200-300 for interpretation Costhelper.com

Guidelines No guidelines available stating when to order an echocardiogram Recent studies involving those with intermediate risk pulmonary emboli have shown the following: PEITHO trial (2014): systemic thrombolysis may prevent hemodynamic decompensation in those with a low bleeding risk ULTIMA trial (2014): ultrasound assisted catheter directed thrombolysis for submassive pulmonary embolism reduces prolonged RV dysfunction compared to heparin alone PEITHO trial: Pulmonary Embolism Thrombolysis ULTIMA trial: Ultrasound Accelerated Thrombolysis of Pulmonary Embolism

Thoughts More studies must be done to address when echocardiograms should be performed to identify submassive pulmonary emboli Should a step wise approach be implemented or a certain number of criteria met before an echocardiogram should be ordered (i.e. postive troponin, dynamic changes in vitals, no clinical improvement, dynamic EKG changes, elevated troponins, number of pulmonary emboli, bilateral involvement, etc.)? More studies addressing risk vs. benefit and developing criteria of when to order echocardiograms need to be performed. We do not want to miss RV dysfunction because developing research suggests these individuals may benefit from systemic catheter directed thrombolysis, but at the same time the cost of doing an echocardiogram in every single individual with a PE may be too great to justify its benefit.

References Jaff, M. R., McMurtry, M. S., Archer, S. L., Cushman, M., Goldenberg, N., Goldhaber, S. Z., ... & Vedantham, S. (2011). Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension a scientific statement from the American Heart Association. Circulation, 123(16), 1788-1830. Cohen, R., Mirrer, B., Loarte, P., Mena, D., & Navarro, V. Echocardiographic Findings in Pulmonary Embolism. Pathophysiology, Evaluation and Management, 73. Grant, R., Erwin, P., & Shishehbor, M. (2015, March 31). Contemporary Management of Acute Pulmonary Embolism: A Focus on Intermediate Risk Patients - American College of Cardiology. Retrieved March 12, 2016, from http://www.acc.org/latest-in- cardiology/articles/2015/03/30/09/03/contemporary-management- of-acute-pulmonary-embolism How Much Does an Echocardiogram Cost? - CostHelper.com. (n.d.). Retrieved March 12, 2016, from http://health.costhelper.com/echocardiograms.html